PMID:15817470

Citation	Chen, YH, Wang, CC, Greenwell, L, Rix, U, Hoffmeister, D, Vining, LC, Rohr, J and Yang, KQ (2005) Functional analyses of oxygenases in jadomycin biosynthesis and identification of JadH as a bifunctional oxygenase/dehydrase. J. Biol. Chem. 280:22508-14
Abstract	A novel angucycline metabolite, 2,3-dehydro-UWM6, was identified in a jadH mutant of Streptomyces venezuelae ISP5230. Both UWM6 and 2,3-dehydro-UWM6 could be converted to jadomycin A or B by a ketosynthase alpha (jadA) mutant of S. venezuelae. These angucycline intermediates were also converted to jadomycin A by transformant of the heterologous host Streptomyces lividans expressing the jadFGH oxygenases in vivo and by its cell-free extracts in vitro; thus the three gene products JadFGH are implicated in catalysis of the post-polyketide synthase biosynthetic reactions converting UWM6 to jadomycin aglycone. Genetic and biochemical analyses indicate that JadH possesses dehydrase activity, not previously associated with polyketide-modifying oxygenase. Since the formation of aromatic polyketides often requires multiple dehydration steps, bifunctionality of oxygenases modifying aromatic polyketides may be a general phenomenon.
Links	PubMed PMC2883817 Online version:10.1074/jbc.M414229200
Keywords	Amino Acid Sequence; Blotting, Southern; Catalysis; Cell-Free System; Escherichia coli/metabolism; Genetic Techniques; Hydro-Lyases/chemistry; Hydro-Lyases/physiology; Isoquinolines/chemistry; Isoquinolines/metabolism; Models, Chemical; Models, Genetic; Molecular Sequence Data; Mutation; Oxygenases/chemistry; Oxygenases/physiology; Protein Binding; Protein Structure, Tertiary; Sequence Analysis, DNA; Species Specificity; Spectrophotometry; Streptomyces/metabolism; Streptomyces lividans/metabolism
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
STRVZ:Q5U913		GO:0016491: oxidoreductase activity	ECO:0000314:		F		Based on table 1; for JadH, both UWM6 and 2,3-dehydro-UWM6 underwent 4a,12b-dehydration and C-12 monooxygenation and were converted to rabelomycin and dehydrorabelomycin, respectively. Rabelomycin remained unchanged. 3) In controls without supplemented enzymes, the substrates remained unchanged.	complete CACAO 4979
STRVZ:Q5U913		GO:0016836: hydro-lyase activity	ECO:0000314:		F		Based on table 1: for JadH, both UWM6 and 2,3-dehydro-UWM6 underwent 4a,12b-dehydration and C-12 monooxygenation and were converted to rabelomycin and dehydrorabelomycin, respectively. Rabelomycin remained unchanged. 3) In controls without supplemented enzymes, the substrates remained unchanged.	complete CACAO 4981
STRVZ:Q5U913	enables	GO:0016491: oxidoreductase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
STRVZ:Q5U913	enables	GO:0016836: hydro-lyase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.